title: Discovery of potent and selective agonists for the free fatty acid receptor 1 (FFA(1)/GPR40), a potential target for the treatment of type II diabetes.
abstract: A series of 4-phenethynyldihydrocinnamic acid agonists of the free fatty acid receptor 1 (FFA(1)) has been discovered and explored. The preferred compound 20 (TUG-424, EC(50) = 32 nM) significantly increased glucose-stimulated insulin secretion at 100 nM and may serve to explore the role of FFA(1) in metabolic diseases such as diabetes or obesity.
authors.affiliation: Department of Physics and Chemistry, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Christiansen
authors.forename: Christian
authors.initials: C
authors.lastname: Urban
authors.forename: Nicole
authors.initials: N
authors.lastname: Merten
authors.forename: Kathrin
authors.initials: K
authors.lastname: Liebscher
authors.forename: Kasper K
authors.initials: KK
authors.lastname: Karlsen
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hamacher
authors.forename: Andreas
authors.initials: A
authors.lastname: Spinrath
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Bond
authors.forename: Christel
authors.initials: C
authors.lastname: Drewke
authors.forename: Susanne
authors.initials: S
authors.lastname: Ullrich
authors.forename: Matthias U
authors.initials: MU
authors.lastname: Kassack
authors.forename: Evi
authors.initials: E
authors.lastname: Kostenis
authors.forename: Trond
authors.initials: T
authors.lastname: Ulven
mesh_terms: D000818:Animals; D002934:Cinnamates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D005947:Glucose / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D002934:Cinnamates; C473034:FFAR1 protein, human; C473036:Ffar1 protein, mouse; C473035:G-protein-coupled receptor 40, rat; D007328:Insulin; D043562:Receptors, G-Protein-Coupled; D005947:Glucose